Dov B. Nudel

Dilated cardiomyopathy complicating a case of epidermolysis bullosa dystrophica.

Abstract: A Child with epidermolysis bullosa dystrophica, recessive type (EBDR) developed significant anemia at 9 years of age and was treated with long‐term transfuslon therapy. At age 17 he had symptoms of congestive heart failure secondary to dilated cardlomyopathy. Treatment with digoxin and vasodilators for the past year has failed to improve his cardiomyopathy significantly. Chronic iron overload and secondary hemosiderosis may have contributed to his problems, and we propose that chelation therapy be used in any child received long‐term transfusion therapy.

Lyme Disease Presenting as Heart Block

Lyme disease is now recognized as an infectious process capable of involving multiple organs including the cardiovascular system. We recently treated a boy whose complaints on admission related only to symptomatic heart block that was severe enough to require transvenous pacing. This boy was subsequently determined to have had Lyme Disease after his medical testing was reevaluated for possible tick exposure. In rare instances symptomatic heart block may be the sole presenting complaint of Lyme Disease in children.

Young Long Distance Runners Physiological and Psychological Characteristics

This study presents the physiological and psychological characteristics and the running histories of 16 subjects who began long distance running at age 4-12 years. Running duration was 3-15 years (mean 8.4 ± 3.6 yrs). Seven children completed 41 marathons, seven 30-mile races, and eight 60-mile races. The other nine competed at shorter distances. All trained at 30-105 miles/week. Two stress fractures, one back sprain and one knee injury occurred. Athletes who reported injuries from recollection may have underreported some injuries. At age 15.4 ± 4.2 years bone age was 15.3 ± 2.6 years and height was at 51 ± 26.0 percentile. Athletes had larger left ventricular diastolic diameter, higher max O 2 uptake, and delayed onset of anaerobic metabolism compared to controls. Psychological profile: IQ = 121 ± 11, scholastic grade point average (GPA) (n = 13) was ≤3.0 in four, 3.6-3.9 in four, and 4.0 in five. Cattell 16 personality factor (PF): Seven scored above the 85th percentile on boldness, warmth, conformity, sensitivity, dominance, and high drive with tension. Eight scored above the 93rd percentile for self discipline and emotional stability. Human Figure Drawing showed a distorted body image in seven. Two developed anorexia nervosa, and another girl committed suicide. Thus, high physical fitness and no growth retardation were observed. These runners, however, shared distinct positive and negative personality characteristics. The relatively high incidence of severe psychological disorders possibly suggests a need for psychological screening for young children entering a strenuous training program and for close monitoring for development of psychological problems during the program.

Cardiac glycoside toxicity in small laboratory animals

Cardiac glycosides are frequently administered to laboratory animals for research purposes. The effects achieved depend not only upon the particular glycoside and dose administered, but also upon an entire array of variables from the species of animal to the temperature of the animal housing facility. We review a number of these factors and their influence upon the effects achieved by the administration of cardiac glycosides to laboratory animals.

Comparative effects of bicarbonate, tris-(hydroxymethyl)aminomethane and dichloroacetate in newborn swine with normoxic lactic acidosis.

A total of 20 newborn piglets age 11.5 +/- 0.3 days and weighing 3.7 +/- 0.1 kg were studied under pentobarbital anesthesia. After stabilization following surgical procedures, baseline values for blood gases, base excess (BE), heart rate (HR), aortic pressure (AoP), left-ventricular contractility (LV dP/dtmax), carotid artery flow (CarF) and renal artery flow (RenF) were measured and normal lactic acid 0.2 ml/kg was infused over 1 h and the same parameters repeated. Then sodium bicarbonate (BC, n = 8), Tris-(hydroxymethyl)aminomethane (THAM, n = 6) or dichloroacetate (DCA, n = 6) were infused over 1 h. The doses of BC and THAM were calculated from the standard formula: Mmol = Base deficit x kg x 0.3. DCA was given at a dose of 300 mg/kg. Following lactic acid infusion, pH was 7.00 +/- 0.4 and BE was -20.6 +/- 1.2. Acidosis was associated with a significant (p < 0.05) increase in AoP (+18.6 +/- 7.4%) and decreases in HR (-13.9 +/- 2.7%) and RenF (-43.8 +/- 10.4%). Values of dP/dtmax and CarF were higher during acidosis in all but 3 animals. Following infusion of alkalizing agents pH and BE values were highest with BC and lowest with DCA and the differences were statistically significant (p < or = 0.05). In general, all three alkalizing agents reversed, in part or completely, the changes in cardiovascular parameters associated with acidosis so that following alkali infusion the changes were not statistically significant when compared to baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of digoxin-amiodarone interaction in the rat.

Abstract Amiodarone and digoxin are often used in combination and clinical experience suggests that amiodarone may increase serum digoxin levels and toxicity. We have investigated the influence of amiodarone on digoxin pharmacokinetics and tissue distribution in the rat. Forty-nine rats were injected with 10 mg/kg amiodarone sc three times a day for 7 days, while 49 others were injected with saline only. On the eighth day, all the rats received 0.5 mg/kg digoxin ip; 4, 5, 6, 7, 8, 10, and 12 hr later, groups of 7 amiodarone-pretreated and control animals were sacrificed, and plasma, heart, liver, muscle, brain, and kidney digoxin concentrations measured by radioimmunoassay. Data were analyzed by two-way ANOVA, with group comparisons using the Waller-Duncan multiple comparison procedure. Digoxin levels were significantly higher in the plasma, heart, muscle, and kidney of the amiodarone-pretreated rats at most points of measurement (P < 0.05) whereas liver digoxin levels were elevated at 8, 10, and 12 hr. Kidney/plasma, heart/plasma, muscle/plasma, and especially liver/plasma ratios in the control groups significantly exceeded the values found in the amiodarone-pretreated group at most time points. Concentrations of digoxin in brain were not changed. This suggests that the volume of distribution is significantly altered in the amiodarone-pretreated group. Amiodarone increases plasma digoxin levels in rats as it does in humans, but the mechanism is unclear.

Comparative effects of bicarbonate and dichloroacetate in newborn swine with hypoxic lactic acidosis.

UNLABELLED Sodium bicarbonate (BC) and dichloroacetate (DCA) were studied in 7- to 14-day-old (n = 25) anesthetized swine with hypoxic acidosis. BC (base deficit X kg X 0.3, n = 10), DCA (300 mg/kg, n = 7) or saline (n = 8) was infused for 1 h. Blood lactic acid, dP/dtmax, heart rate and cardiac output increased and base excess and total arterial and carotid resistances (R) decreased with acidosis; aortic pressure, renal and mesenteric R did not change. BC induced higher pH, base excess and lactic acid. Heart rate in all and dP/dtmax with BC and DCA were restored; renal and mesenteric R and aortic pressure decreased in all. Cardiovascular responses to DCA and BC did not differ except for renal R. CONCLUSION BC is a more effective alkalizer than DCA, which induced a greater renal vasodilation; both restored contractility.

14 EXERCISE PERFORMANCE OF ADOLESCENTS WITH ESSENTIAL HYPERTENSION

Eight adolescent patients, 7 boys(15-19 yrs.) and a 13 y. old girl with essential hypertension of 1-5 years duration(mean 3 y.) were studied. Blood pressure(BP) ranged 150-170/95-110 at rest and none received any medication. Simple progressive exercise on a bicycle ergometer with increments of 25 Watt(W) every minute were performed until limited by fatigue. Expired air was measured with a pneumotach and integrated to minute ventilation. Fractional concentration of mixed expired gas was analyzed with a rapid responding O2 analyzer. Oxygen consumption was calculated from the minute ventilation(STPD) and mixed exhaled O2. Seven patients reached ≥95% of predicted maximal heart rate. Maximal systolic BP ranged 165-240mm Hg.(mean 199). Diastolic BP increased in 1, did not change in 5, and decreased in 2. Maximal working capacity(Wmax) ranged 150-200 W. Maximal oxygen uptake (MVO2) was 2060 ml/min in the girl and 2535-3464 ml/min(mean 3072) for the boys(mean MVO2 41.6 ml/kg/min). Anerobic threshold (AT) occurred at 100-175 W(mean 134) which was 50-88% of Wmax (mean at 81%). None of the patients had chest pain or ECG abnormalities. These preliminary data suggest that, in the majority, BP does not rise to very high levels, strenuous exercise can be permitted but Wmax is at the low normal range in spite of normal AT.

The Effect of Hemodialysis on the Left Ventricular Systolic and Diastolic Function in Children and Adolescents with End Stage Renal Disease 1810

The Effect of Hemodialysis on the Left Ventricular Systolic and Diastolic Function in Children and Adolescents with End Stage Renal Disease 1810

180 HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM) IN NEW- BORN AND EARLY INFANCY PERIOD

Clinical course and diagnostic studies in 6 infants under 8 weeks with HOCM are presented. One presented with severe CHF, one with severe arrhythmias; both died. In 4, findings were subtle; VSD-like murmurs, mild tachypnea and cardiomegaly. ECGs showed a superior axis in 5 and WPW in 1. Initial M-mode echos were inconclusive. Sector Scans done on 3 were diagnostic in 1, but became more specific at a later age. Cardiac catheterization (CC) was performed at age 1-49 (mean 18) days. Initial resting LV-AO gradient was 50±11 (n=5). Three showed the Brockenbrough response and in 2 no adequate post ectopic beat was recorded. Angiography showed severe septal hypertrophy, hypercontractility, distortion of LV cavity and compression of RV. In 4, the mitral valve (MV) was visualized and showed SAM. In 1 an additional fixed subaortic obstruction was suspected. A second CC in the survivors 18±4.25 mos. later showed a larger gradient, 80±8.17 in 3, and an unchanged gradient in 1. Followup period was 9-54 (mean 23) mos. and all survivors are well on beta blockers. Diagnosis was confirmed at autopsy in 2 and surgery in 1. Conclusion: 1) Prognosis was not related to pressure gradients. 2) Those presented with severe symptoms died. 3) Since physical findings, ECGs and echos in this age are atypical, a high index of suspicion and possibly CC is needed for accurate assessment.